Finally, the human Entrez Gene identifiers were mapped to the appropriate Affymetrix U133 2. 0 plus probe set ID read more using the Affymetrix U133 2. 0 plus annotation version 31 data file. Biomarker rules This method uses simple binary logic biomarker rules to indicate or contraindicate specific agents. The bio marker rules are established on the basis of vetted litera ture and compiled in a database in the simple form IF biomarker expressed or predefined Z score value THEN DO or DO NOT recommend drug. While each biomarker drug rule can be weighted on the basis of the disease con text of published findings, the iteration of the system used in this study assumed equal weighting for all biomarker rules irrespective on disease context would be utilized in this feasibility study.

Drug target Inhibitors,Modulators,Libraries expression This is analogous to the biomarker rules approach de scribed above except Inhibitors,Modulators,Libraries that it relies exclusively on the known mechanism of action of each agent, and does not require well vetted literature to demonstrate an association be tween the expression of the drug target and the drugs efficacy. This method utilizes a human drug Inhibitors,Modulators,Libraries target knowledge base developed from various sources including DrugBank, MetaCore, MedTrack, PharmGKB, UpToDate and DrugDex. In this study, drug tar gets found to be over expressed in a patients tumor relative to the refer ence set were identified along with the agent that inhibits the targets activity. Drug response signatures The Connectivity Map concept was initially developed by the Broad Institute in an attempt to connect molecu lar signatures of disease with drug induced changes in gene expression.

drugs that are shown to induce changes in gene expression in a set of cancer cell lines which reverse the disease associated DEGs towards nor mal levels are identified as therapeutic candidates. In our study, the maximum number of DEGs submitted Inhibitors,Modulators,Libraries to this algorithm were capped at 500 and the method used rank based statistics to identify Inhibitors,Modulators,Libraries selleck screening library candidate drugs as described previously. Drug sensitivity signatures This method adopts Parametric Gene Set Enrichment Analysis using the NCI 60 cell line drug sensitiv ity signatures. Gene expression signatures associated with differential response to specific drugs on the basis of the NCI 60 cell line in vitro drug screen are compared to the tumor derived gene expression signature. This approach is consistent with well published methods for inferring drug sensitivity utilizing the NCI 60 cell line dataset and baseline gene expression signatures. Network target activity This method predicts the activity level of drug targets on the basis of a specific type of molecular network analysis referred to as topological analysis which has been described previously.